Unique MAP Kinase binding sites

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Map kinases are drug targets for autoimmune disease, cancer, and apoptosis-related diseases. Drug discovery efforts have developed MAP kinase inhibitors directed toward the ATP binding site and neighboring "DFG-out" site, both of which are targets for inhibitors of other protein kinases. On the other hand, MAP kinases have unique substrate and small molecule binding sites that could serve as inhibition sites. The substrate and processing enzyme D-motif binding site is present in all MAP kinases, and has many features of a good small molecule binding site. Further, the MAP kinase p38α has a binding site near its C-terminus discovered in crystallographic studies. Finally, the MAP kinases ERK2 and p38α have a second substrate binding site, the FXFP binding site that is exposed in active ERK2 and the D-motif peptide induced conformation of MAP kinases. Crystallographic evidence of these latter two binding sites is presented.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number1
DOIs
StatePublished - Jan 2008

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Phosphotransferases
Binding Sites
p38 Mitogen-Activated Protein Kinases
4 alpha-glucanotransferase
Substrates
Molecules
Drug Discovery
Protein Kinase Inhibitors
Protein Kinases
Autoimmune Diseases
Conformations
Adenosine Triphosphate
Apoptosis
Peptides
Processing
Pharmaceutical Preparations
Neoplasms

Keywords

  • FXFP
  • Inhibitor binding
  • MAP kinases
  • PD98059
  • Sulindac
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics

Cite this

Unique MAP Kinase binding sites. / Akella, Radha; Moon, Thomas M.; Goldsmith, Elizabeth J.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1784, No. 1, 01.2008, p. 48-55.

Research output: Contribution to journalArticle

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